Immunotherapeutic strategies for high-risk bladder cancer

Abstract

Transitional cell carcinoma (TCC), which is the pathological diagnosis for the majority of bladder cancers, is a solid tumor entity that is responsive to immunotherapy as evidenced by a substantial cure rate documented with the use of intravesical bacillus Calmette-Guérin (BCG) therapy in selected patients with high-grade superficial disease. The nonspecific immune modulation that occurs as a result of BCG therapy is not well understood; however, the success of BCG therapy provides a basis for the exploration of mechanisms related to immune responses and the development of novel immunotherapeutic agents for the treatment of high-risk disease. In this review, we discuss the complexity of the immune system and therapies that are considered capable of manipulating it to potentially benefit patients with bladder cancer.

Figure 1

Antigen is presented in the context of major histocompatibility (MHC) molecules to T-cell receptor (TCR), referred to as signal 1, and costimulatory molecules, such as CD28 and B7, provide signal 2 to allow for T-cell activation. T-cell responses are then regulated by CTLA4 interaction with B7 so as to maintain homeostasis. Regulatory T cells can also suppress T-cell activation. In cancer patients, it is possible to interfere with the CTLA4-B7 interactions with anti-CTLA4 antibody thereby promoting enhanced T-cell responses.